GENRE2: GENetic Risk Estimation of Breast Cancer Prior to Decisions on Preventive Therapy Uptake, Risk Reducing Surgery or Intensive Imaging Surveillance

Sponsor

Mayo Clinic (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04474834

Collaborator

(none)

900

Enrollment

Locations

62.5

Anticipated Duration (Months)

180

Patients Per Site

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary aim of this study is to determine if the addition of an individual polygenic risk score (PRS) in addition to the Breast Cancer Risk Assessment Tool (BCRAT) or Tyrer-Cuzick (IBIS) score will aid women at risk of breast cancer in making a decision to take (or not take) medications to prevent breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Genetic: Polygenic Risk Score

Detailed Description

This is a minimal risk prospective multisite study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the availability of the PRS influenced patient decisions regarding preventive medicine and medication compliance. Because women know beforehand that the PRS is pending, study participants will be advised that a final decision to take preventive medicine must be deferred until after the PRS results are made available. Nevertheless, a survey of understanding of risk and benefit and assessment of willingness to take preventive medicine will be done prior to receiving the PRS results and then another survey will be completed after receiving the PRS score.

Study Design

Study Type:

Observational

Anticipated Enrollment :

900 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

GENetic Risk Estimation of Breast Cancer Prior to Decisions on Preventive Therapy Uptake, Risk Reducing Surgery or Intensive Imaging Surveillance: A Study to Determine if a Polygenic Risk Score Influences the Decision Making Options Amongst High Risk Women (GENRE 2)

Actual Study Start Date :

Oct 17, 2019

Anticipated Primary Completion Date :

Jul 31, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
PRS Providing polygenic risk score (PRS)	Genetic: Polygenic Risk Score A Polygenic Risk Score (PRS) is a blood based genetic test which assesses 300 common breast cancer susceptibility loci (Single Nucleotide Polymorphisms). The PRS has been retrospectively validated and categorizes women into three categories of lifetime risk of developing breast cancer: Low Risk (<15% lifetime risk), Above Average Risk (15 to 40%), and high risk (>40 %).

Arm

Intervention/Treatment

PRS

Providing polygenic risk score (PRS)

Genetic: Polygenic Risk Score

A Polygenic Risk Score (PRS) is a blood based genetic test which assesses 300 common breast cancer susceptibility loci (Single Nucleotide Polymorphisms). The PRS has been retrospectively validated and categorizes women into three categories of lifetime risk of developing breast cancer: Low Risk (<15% lifetime risk), Above Average Risk (15 to 40%), and high risk (>40 %).

Outcome Measures

Primary Outcome Measures

Patient self-reported intention to take a breast cancer preventing medication [up to 6 months after initial consultation]

Secondary Outcome Measures

Proportion of patients who are taking preventative medications each year for 10 years [Each year for up to 10 years]
Endocrine related quality of life scores each year for 10 years [Each year for up to 10 years]
Proportion of patient who are pursuing supplemental screening for 10 years [Each year for up to 10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Women > 35 years old and < 75 years old
Women with any of the following:

A NCI-BCRAT 5 year risk of ≥ 3% which corresponds to the level in which there is moderate evidence of treatment benefit outweighing risk according to the US Preventative Services Task Force (32); or B. IBIS (Tyrer-Cuzik) score for the 10 year risk of breast cancer of ≥8% 43 C. Biopsy proven atypical ductal hyperplasia or atypical lobular hyperplasia. D. History of lobular carcinoma in situ E. BRCA mutation carrier or other hereditary breast mutation carrier

Able to participate in all aspects of the study
Understand and signed the study informed consent

Exclusion Criteria:

Women whose BCRAT falls below the threshold (<3 % 5 year risk) of moderate benefit according to the US Preventative Task Force AND Women whose IBIS score is <8% for the 10 year risk
Women with known contra-indications to Tamoxifen, raloxifene ,exemestane, or anastrazole
Current or prior use of Tamoxifen, raloxifene, exemestane or anastrazole
Unable to give informed consent
Prior history of invasive breast cancer, ductal carcinoma in situ or other breast cancers
At high risk due to prior radiation therapy to the chest
Women who are pregnant or breastfeeding
Prior risk reducing or prophylactic mastectomy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259
2	Mayo Clinic	Jacksonville	Florida	United States	32224-9980
3	Northwestern University	Evanston	Illinois	United States	60208
4	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
5	Cleveland Clinic	Cleveland	Ohio	United States	44195